Neutrophil Gelatinase Associated Lipocalin Is an Early and Accurate Biomarker of Graft Function and Tissue Regeneration in Kidney Transplantation from Extended Criteria Donors
Abstract:BackgroundDelayed graft function (DGF) is an early complication of kidney transplantation (KT) associated with increased risk of early loss of graft function. DGF increases using kidneys from extended criteria donors (ECD). NGAL is a 25KDa protein proposed as biomarker of acute kidney injury. The aim of this study was to investigate the role of NGAL as an early and accurate indicator of DGF and Tacrolimus (Tac) toxicity and as a mediator of tissue regeneration in KT from ECD.MethodsWe evaluated plasma levels o… Show more
“…Use of TAC in kidney‐transplant recipients, resulted in a significant rise in NGAL levels without any changes in serum creatinine . In a cohort of 80 kidney‐transplant patients, of whom all used CyA, NGAL levels were significantly higher when compared to CKD patients stages 2‐4 and healthy volunteers and was associated to the dose of CyA .…”
Section: Discussionmentioning
confidence: 98%
“…Delayed graft function (DGF) may be regarded as a form of AKI occurring after kidney transplantation usually defined as the need for dialysis during the first week after transplantation. NGAL levels were significantly higher in patients with DGF day 1 after transplantation compared to those who did not require dialysis in a study of 50 kidney transplant recipients from extended criteria donors . The acute rise in NGAL levels has been hypothesized as essential for protection against infection and as part of the regenerative proliferation that follows an AKI .…”
The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored.
“…Use of TAC in kidney‐transplant recipients, resulted in a significant rise in NGAL levels without any changes in serum creatinine . In a cohort of 80 kidney‐transplant patients, of whom all used CyA, NGAL levels were significantly higher when compared to CKD patients stages 2‐4 and healthy volunteers and was associated to the dose of CyA .…”
Section: Discussionmentioning
confidence: 98%
“…Delayed graft function (DGF) may be regarded as a form of AKI occurring after kidney transplantation usually defined as the need for dialysis during the first week after transplantation. NGAL levels were significantly higher in patients with DGF day 1 after transplantation compared to those who did not require dialysis in a study of 50 kidney transplant recipients from extended criteria donors . The acute rise in NGAL levels has been hypothesized as essential for protection against infection and as part of the regenerative proliferation that follows an AKI .…”
The median levels of iFGF23 were higher in CNI users compared to CNI nonusers giving support to the notion of a CNI induced FGF23 resistance in the parathyroid. The net result of CNIs side effects needs to be further explored.
“…Indeed, IRI involves a complex interplay between leukocyte activation, autophagy, complement activation, oxidative stress, and endothelial cell injury [31]. Several biomarkers including serum NGAL [32,33], urine NGAL [34,35], urine interleukine-18 [34,35], urine clustering [36], and urine insulin-like growth factor-binding protein-7 and tissue inhibitor of metalloproteinases-2 [37] could affect the above mechanisms and showed promising results of AUC for predicting DGF, ranging from 0.7 to 0.9, depending on the timing of biomarkers sampling and the definition of DGF. In the present study, the FST outperformed urine NGAL, RI of renal arteries, and ERPF in the prediction of DGF (Table 3).…”
Background: Delayed graft function (DGF) could worsen early and long-term outcomes of kidney transplantation (KT). DGF is caused by several pre-transplantation and perioperative factors in both donors and recipients. At present, there are no biomarkers or tests during the immediate post-KT period that can accurately predict the development of DGF. Materials and methods: This prospective study was conducted in deceased donor KT (DDKT) at King Chulalongkorn Memorial Hospital, Thailand. All recipients underwent furosemide stress test (FST) by receiving a single dose of intravenous furosemide, 1.5 mg/kg at 3 h after allograft reperfusion. We determined the correlations between DGF (requiring dialysis within the first week after transplantation) and the values of urine volume recorded hourly after FST until 6 h, the parameters of postoperative dynamic tests, including resistive index (RI) of renal arteries and effective renal plasma flow (ERPF), and urine neutrophil gelatinase-associated lipocalin (NGAL). Results: Of the 59 total DDKT recipients enrolled, 24 developed DGF. The FST is a more accurate biomarker than urine NGAL, RI of renal arteries, and ERPF in the prediction of DGF. The 4-h urine volume less than 350 mL (FST non-responsive) was the best cut-off value in predicting DGF with 87.5% sensitivity, 82.9% specificity, and 82.5% accuracy. Multiple logistic regression analyses showed an odds ratio of 0.993 (0.986–0.999, p = 0.035) for the 4-h urine volume to predict DGF. Conclusions: The FST is a simple and accurate biomarker for predicting DGF in early post-KT period. Close monitoring and well prepared dialysis are suggested in patients with urine volume < 350 mL after 4 h of FST. The FST non-responsive patients could be the target for further DGF preventive intervention. ClinicalTrials.gov identifier: NCT03071536.
“…HIF1A upregulation along with HMOX1 activation after donor preconditioning with fenoldopam was shown to have positive effects on renal function in a rat kidney transplantation model. 43,44 The reader is referred to a review on ischaemic kidney injury and mechanisms of tissue repair by El Sabbahy and Vaidya, who discuss mechanisms of ischaemic injury and repair in acute and chronic kidney diseases. Part of these effects could be attributed to a downregulation of miR-127-3p.…”
We have generated a set of renoprotective factors based on the literature information, which was functionally annotated and evaluated with respect to tested compounds in kidney disease and diabetes clinical trials.
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